tbuckley/cabot-search huggingface dataset:
Expression of the readthrough transcript CiDRE in alveolar macrophages boosts SARS-CoV-2 susceptibility and promotes COVID-19 severity
Authors: Yuichi Mitsui, Tatsuya Suzuki, Kanako Kuniyoshi, Jun Inamo, Kensuke Yamaguchi, Mariko Komuro, Junya Watanabe, Mio Edamoto, Songling Li, Tsukasa Kouno, Seiya Oba, Tadashi Hosoya, Kentaro Masuhiro, Yujiro Naito, Shohei Koyama, Nobuo Sakaguchi, Daron M. Standley, Jay W. Shin, Shizuo Akira, Shinsuke Yasuda, Yasunari Miyazaki, Yuta Kochi, Atsushi Kumanogoh, Toru Okamoto, Takashi Satoh
Journal: Immunity (2023)
Customization of the translational complex regulates mRNA-specific translation to control CNS regeneration
Authors: Julia Schaeffer, Noemie Vilallongue, Charlotte Decourt, Beatrice Blot, Nacera El Bakdouri, Elise Plissonnier, Blandine Excoffier, Antoine Paccard, Jean-Jacques Diaz, Sandrine Humbert, Frederic Catez, Frederic Saudou, Homaira Nawabi, Stephane Belin
Journal: Neuron (2023)

In the adult mammalian central nervous system (CNS), axons fail to regenerate spontaneously after injury because of a combination of extrinsic and intrinsic factors. Despite recent advances targeting the intrinsic regenerative properties of adult neurons, the molecular mechanisms underlying axon regeneration are not fully understood. Here, we uncover a regulatory mechanism that controls the expression of key proteins involved in regeneration at the translational level. Our results show that mRNA-specific translation is critical for promoting axon regeneration. Indeed, we demonstrate that specific ribosome-interacting proteins, such as the protein Huntingtin (HTT), selectively control the translation of a specific subset of mRNAs. Moreover, modulating the expression of these translationally regulated mRNAs is crucial for promoting axon regeneration. Altogether, our findings highlight that selective translation through the customization of the translational complex is a key mechanism of axon regeneration with major implications in the development of therapeutic strategies for CNS repair.
Sampling a wide swathe of primate genetic diversity
Authors: Evan E. Eichler
Journal: Cell Genomics (2023)

Two studies published in Science report the deepest survey of primate genetic diversity using short-read sequencing to sample ∼47% of extant species. Kuderna et al.1 investigate genetic diversity, mutation rates, and our primate phylogeny, while Gao et al.2 use the data to better classify disease-causing mutations.
Let’s find a way to work together
Journal: BMJ (2023)

Let's find a way to work together Myrian describes how an acquired brain injury has affected her, and the challenges she now faces when engaging in healthcare consultationsIn 2015 I experienced varicella zoster virus meningoencephalitis and was left with an acquired brain injury.The fallout has affected every area of my life, and is impossible to predict.I was unprepared for the downward spiral that my brain and body would enter.I have had more than 30 MRI, PET, and CT scans, as well as x ray imaging, multiple biopsies, a lifesaving ileostomy, and more than 400 vials of blood taken.
Intestinal mucus and their glycans: A habitat for thriving microbiota
Authors: Ana S. Luis, Gunnar C. Hansson
Journal: Cell Host & Microbe (2023)

The colon mucus layer is organized with an inner colon mucus layer that is impenetrable to bacteria and an outer mucus layer that is expanded to allow microbiota colonization. A major component of mucus is MUC2, a glycoprotein that is extensively decorated, especially with O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation and making mucus. Some microbiota members are known to encode multiple proteins that are predicted to bind and/or cleave mucin glycans. The interactions between commensal microbiota and host mucins drive intestinal colonization, while at the same time, the microbiota can utilize the glycans on mucins and affect the colonic mucus properties. This review will examine this interaction between commensal microbes and intestinal mucins and discuss how this interplay affects health and disease.
Difficulties of Diagnosing Primary Multiple Synchronous Breast Cancer with Histological Heterogeneity of Tumors (Clinical Case)
Authors: O. O. Manuylova, E. V. Shivilov, T. V. Pavlova
Journal: Radiology - Practice (2023)

The difficulties of timely diagnosis of primary multiple synchronous breast cancer with histological heterogeneity of tumors are demonstrated by a clinical example. Taking into account the fact that breast cancer continues to lead among all oncological pathology and accounts for 11.8% of all malignant neoplasms, diagnostic algorithms of the stage should be personalized. The presented clinical case demonstrates multidisciplinary errors committed at different stages of the patient’s examination.
On the Introduction of Artificial Intelligence into the Daily Practice of Breast Pathology Diagnosis: has Everything been Taken into Account?
Authors: V. A. Kazakova, E. V. Shivilov, K. A. Anichkina, S. A. Tyulyakova, A. V. Pasternak
Journal: Radiology - Practice (2023)

Artificial Intelligence (AI) has the potential to improve the diagnosis and effectiveness of breast cancer treatment. However, the use of AI in medicine in general, and in mammology in particular, requires regulation by legislative and legal acts to ensure the protection of patients’ rights, safety and quality of medical care. Special attention should be paid to the training of medical personnel and the development of new technologies and methods of working with AI. There are laws and regulations governing the use of AI in mammology around the world. This article reviews the laws governing the use of AI in breast radiology in Western Europe, Asia, and the United States.
Contrast Enhanced Spectral Mammography as the Method of Choice in the Diagnosis of Breast Cancer in Young Women
Authors: A. V. Chernaya, R. Kh. Ul’yanova, S. S. Bagnenko, P. V. Krivorot’ko, S. N. Novikov, A. N. Zaytsev
Journal: Radiology - Practice (2023)

Breast cancer (BC) in young women is cancer that has developed in women aged less than 40 years. Purpose of this study was to compare the overall diagnostic performance of CESM and digital mammography (DM) in detecting breast cancer in women under 40 years. The study group included 75 patients. When analyzing the data obtained, all indicators of diagnostic effectiveness in CESM statistically significantly exceeded the DM data. Thus, due to the ability to assess vascularization, CESM is characterized by higher sensitivity in the diagnosis of breast cancer in young women comparing to DM.
Ductal Carcinoma in situ in Combination with Inflammatory Breast Syndrome: the Rare Clinical Case
Authors: T. V. Pavlova, E. V. Shivilov, K. A. Anichkina, D. D. Yurkanova, N. S. Karnaukhov
Journal: Radiology - Practice (2023)

Ductal carcinoma in situ (DCIS) is a breast carcinoma (BC) consisting of malignant cells in the ductal lumen of the breast without invasion beyond the epithelial membrane. The article presents a rare clinical case of the combined course of chronic mastitis and ductal carcinoma in situ in a 47-year-old female patient who was diagnosed with chronic mastitis during instrumental examination, and only after trepan biopsy and subsequent histological examination, intraductal breast cancer in situ was verified. This may indicate that instrumental methods and techniques are insufficiently informative in diagnosing ductal carcinoma in situ against the background of chronic mastitis.
BI-RADS 3 — Observation or Action? (lecture)
Authors: N. V. Klimova, A. A. Kuznetsov
Journal: Radiology - Practice (2023)

Breast cancer is an important medical and social problem.A significant factor in reducing mortality and disability in breast cancer is the organization ofqualified assistance, and its integral part is highquality diagnostics.The lecture discusses the practice of applying one of the categories in the system of descriptionand processing of breast research data.Recommendations are given to improve the diagnosis and routing of patients with breast cancer.
An injectable conductive hydrogel with dual responsive release of rosmarinic acid improves cardiac function and promotes repair after myocardial infarction
Authors: Linghong Zhang, Zhongwu Bei, Tao Li, Zhiyong Qian
Journal: Bioactive Materials (2023)

Myocardial infarction (MI) causes irreversible damage to the heart muscle, seriously threatening the lives of patients. Injectable hydrogels have attracted extensive attention in the treatment of MI. By promoting the coupling of mechanical and electrical signals between cardiomyocytes, combined with synergistic therapeutic strategies targeting the pathological processes of inflammation, proliferation, and fibrotic remodeling after MI, it is expected to improve the therapeutic effect. In this study, a pH/ROS dual-responsive injectable hydrogel was developed by modifying xanthan gum and gelatin with reversible imine bond and boronic ester bond double crosslinking. By encapsulating polydopamine-rosmarinic acid nanoparticles to achieve on-demand drug release in response to the microenvironment of MI, thereby exerting anti-inflammatory, anti-apoptotic, and anti-fibrosis effects. By adding conductive composites to improve the conductivity and mechanical strength of the hydrogel, restore electrical signal transmission in the infarct area, promote synchronous contraction of cardiomyocytes, avoid induced arrhythmias, and induce angiogenesis. Furthermore, the multifunctional hydrogel promoted the expression of cardiac-specific markers to restore cardiac function after MI. The in vivo and in vitro results demonstrate the effectiveness of this synergistic comprehensive treatment strategy in MI treatment, showing great application potential to promote the repair of infarcted hearts.
In Utero Exposure to Phenobarbital and Intelligence Deficits in Adult Men
Authors: June Machover Reinisch, Stephanie A. Sanders, Erik Lykke Mortensen, Donald B. Rubin
Journal: JAMA (1995)

<h3>Objective.</h3> —To test whether exposure to phenobarbital in utero is associated with deficits in intelligence scores in adult men and whether the magnitude of the postnatal effect is mediated by exposure parameters and/or postnatal environmental factors. <h3>Design.</h3> —Two double-blind studies were conducted on independent samples of adult men prenatally exposed to phenobarbital and matched control samples using different measures of general intelligence. Based on data from control subjects, regression models were built relating intelligence scores to relevant pre-exposure matching variables and age at testing. Models generated predicted scores for each exposed subject. Group mean differences between the individually predicted and observed scores estimated exposure effects. <h3>Setting.</h3> —Copenhagen, Denmark. <h3>Participants.</h3> —Exposed subjects were adult men born at the largest hospital in Copenhagen between 1959 and 1961 who were exposed to phenobarbital during gestation via maternal medical treatment and whose mothers had no history of a central nervous system disorder and no treatment during pregnancy with any other psychopharmacological drug. Study 1 included 33 men and study 2,81 men. Controls were unexposed members of the same birth cohort matched on a wide spectrum of maternal variables recorded prenatally and perinatally. Controls for studies 1 and 2 included 52 and 101 men, respectively. <h3>Main Outcome Measures.</h3> —In study 1: Wechsler Adult Intelligence Scale (Danish version); in study 2: Danish Military Draft Board Intelligence Test (Børge Priens Prove). <h3>Result.</h3> —Men exposed prenatally to phenobarbital had significantly lower verbal intelligence scores (approximately 0.5 SD) than predicted. Lower socioeconomic status and being the offspring of an "unwanted" pregnancy increased the magnitude of the negative effects. Exposure that included the last trimester was the most detrimental. <h3>Conclusion.</h3> —Phenobarbital exposure during early development can have long-term deleterious effects on cognitive performance. Detrimental environmental conditions can interact with prenatal biological insult to magnify negative outcomes. Physicians are urged to use increased caution in prescribing such medications during pregnancy. (<i>JAMA</i>. 1995;274:1518-1525)
Biomarkers to Guide Medical Therapy in Primary Aldosteronism
Authors: Gregory L Hundemer, Alexander A Leung, Gregory A Kline, Jenifer M Brown, Adina F Turcu, Anand Vaidya
Journal: Endocrine Reviews (2023)

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.
Global assessment of promoter methylation in a mouse model of cancer identifies ID4 as a putative tumor-suppressor gene in human leukemia
Authors: Li Yu, Chunhui Liu, Jeff Vandeusen, Brian Becknell, Zunyan Dai, Yue-Zhong Wu, Aparna Raval, Te-Hui Liu, Wei Ding, Charlene Mao, Shujun Liu, Laura T Smith, Stephen Lee, Laura Rassenti, Guido Marcucci, John Byrd, Michael A Caligiuri, Christoph Plass
Journal: Nature Genetics (2005)
Outpatient Oral Antibiotics for Febrile Neutropenic Cancer Patients Using a Score Predictive for Complications
Authors: Jean Klastersky, Marianne Paesmans, Aspasia Georgala, Frédérique Muanza, Barbara Plehiers, Laurent Dubreucq, Yassine Lalami, Michel Aoun, Martine Barette
Journal: Journal of Clinical Oncology (2006)

Purpose Since febrile neutropenic patients were recognized to constitute a heterogeneous population, several models have been developed for predicting the risk of serious medical complications. The Multinational Association for Supportive Care in Cancer score and its derived clinical prediction rules have been validated, but thus far there were no data about its use for simplifying therapy in predicted low-risk patients. Patients and Methods In a single institution, we followed all episodes of febrile neutropenia between January 1999 and November 2003. Those patients predicted at low risk for complications, who were not receiving antibacterials at fever onset and were eligible for treatment with oral antibiotics, were treated with ciprofloxacin and amoxicillin-clavulanate and were discharged if they were clinically stable or improving after an initial observation period. The primary end point of the study was the rate of resolution of the febrile neutropenic episode without complications, among these early discharged patients. Results Of 383 first febrile neutropenic episodes predicted at low risk of omplication, 178 patients (33 men and 145 women, mainly with solid tumors) were treated orally; they constituted the basis of our analysis. Seventy-nine patients (44%) were discharged early (with a median time to discharge of 26 hours); no complications occurred among them but three patients had to be readmitted, resulting in a success rate of 96% (95% CI, 92% to 100%). Conclusion Our study shows that oral therapy followed by early discharge was feasible in a small but significant proportion of patients selected by a strategy combining predicted low risk and medical and nonmedical criteria.
The cIAP ubiquitin ligases sustain type 3 γδ T cells and ILC during aging to promote barrier immunity
Authors: John Rizk, Urs M. Mörbe, Rasmus Agerholm, Maria Virginia Baglioni, Elisa Catafal Tardos, Marcelo Gregorio Filho Fares da Silva, Isabel Ulmert, Darshana Kadekar, Monica Torrellas Viñals, Vasileios Bekiaris
Journal: The Journal of Experimental Medicine (2023)

Early-life cues shape the immune system during adulthood. However, early-life signaling pathways and their temporal functions are not well understood. Herein, we demonstrate that the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2), which are E3 ubiquitin ligases, sustain interleukin (IL)-17–producing γ δ T cells (γδT17) and group 3 innate lymphoid cells (ILC3) during late neonatal and prepubescent life. We show that cell-intrinsic deficiency of cIAP1/2 at 3–4 wk of life leads to downregulation of the transcription factors cMAF and RORγt and failure to enter the cell cycle, followed by progressive loss of γδT17 cells and ILC3 during aging. Mice deficient in cIAP1/2 have severely reduced γδT17 cells and ILC3, present with suboptimal γδT17 responses in the skin, lack intestinal isolated lymphoid follicles, and cannot control intestinal bacterial infection. Mechanistically, these effects appear to be dependent on overt activation of the non-canonical NF-κB pathway. Our data identify cIAP1/2 as early-life molecular switches that establish effective type 3 immunity during aging.
Contextualizing the Price of Biosimilar Adalimumab Based on Historical Rebates for the Original Formulation of Branded Adalimumab
Authors: Sean R. Dickson, Nico Gabriel, Inmaculada Hernandez
Journal: JAMA Network Open (2023)

This cross-sectional study compares recent list and net prices for Humira after rebates with announced prices of interchangeable biosimilar Humira formulations.
<scp>CLA</scp><sup>+</sup> memory T cells in atopic dermatitis
Authors: Lídia Sans‐de San Nicolàs, Tali Czarnowicki, Mübeccel Akdis, Ramon M. Pujol, Daniel Lozano‐Ojalvo, Donald Y. M. Leung, Emma Guttman‐Yassky, Luis F. Santamaria‐Babí
Journal: Allergy (2023)

Abstract Circulating skin‐homing cutaneous lymphocyte‐associated antigen (CLA) + T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL‐13, IL‐31, pruritus, CCL17 and early effects on dupilumab‐treated patients have in common that they are associated with the CLA + T cell mechanisms in atopic dermatitis patients. The function of CLA + T cells corresponds with the role of T cells belonging to the skin‐associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology.
STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment–Elevation Myocardial Infarction: A Randomized, Open-Label Trial
Authors: Frans Van de Werf, Arsen D. Ristić, Oleg V. Averkov, Alexandra Arias-Mendoza, Yves Lambert, José F. Kerr Saraiva, Pablo Sepulveda, Fernando Rosell-Ortiz, John K. French, Ljilja B. Musić, Katleen Vandenberghe, Kris Bogaerts, Cynthia M. Westerhout, Alain Pagès, Thierry Danays, Kevin R. Bainey, Peter Sinnaeve, Patrick Goldstein, Robert C. Welsh, Paul W. Armstrong
Journal: Circulation (2023)

ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown.
Development and Multicenter Case–Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction
Authors: Keyan Salari, Debasish Sundi, Jason J. Lee, Shulin Wu, Chin-Lee Wu, Gabrielle DiFiore, Q. Robert Yan, Andrew Pienkny, Chi K. Lee, Daniel Oberlin, Greg Barme, Joel Piser, Robert Kahn, Edward Collins, Kevin G. Phillips, Vincent M. Caruso, Mahdi Goudarzi, Monica Garcia-Ransom, Peter S. Lentz, Martha E. Evans-Holm, Andrew R. MacBride, Daniel S. Fischer, Iden J. Haddadzadeh, Brian C. Mazzarella, Joe W. Gray, Theresa M. Koppie, Vincent T. Bicocca, Trevor G. Levin, Yair Lotan, Adam S. Feldman
Journal: Clinical Cancer Research (2023)

Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk.This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology.uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%.uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.